Changes in Graves’ Ophthalmopathy after Radioiodine and Anti-Thyroid Drug Treatment of Graves’ Disease from 2 Prospective, Randomized, Open-Label, Blinded End Point Studies

Abstract

Aims:

A significant association between radioiodine therapy (RIT) and the development or the worsening of pre-existing Graves’ ophthalmopathy (GO) has been reported. This post-hoc analysis of 2 studies attempted to describe the changes observed in pre-existing or new-onset GO following RIT with the goal of euthyroidism rather than hypothyroidism and to describe the relationship GO changes and the final outcome.

Patients and Methods:

In 2 prospective, randomized open-label blinded endpoint trials, patients received radioiodine alone; or, patients received radioiodine or antithyroid drug therapy (ATD). The severity and activity of GO were assessed during a 9–12-year follow-up. The study end points in study 1 were euthyroidism, hyperthyroidism, hypothyroidism, and changes in GO. In study 2, the end points were euthyroidism, hyperthyroidism, hypothyroidism, relapse, and changes in GO.

Results:

Both RIT and ATD were associated with worsening GO and new-onset GO. Both RIT and ATD led to similar aggravation of pre-existing GO or the development to new-onset GO. After RIT or ATD, the euthyroid patients (without levothyroxine substitution) demonstrated an improvement in GO, with 78–89% patients with preexisting GO exhibiting improvement, whereas hyperthyroid, hypothyroid and relapsed patients had worsening or new-onset GO.

Conclusions:

Thyroid function is a dominant risk factor. Thyroid function may be the most important determinant in worsening or new-onset GO in both the natural disease course and in treated patients, independent of the kind of treatment. Therefore, we recommend euthyroidism as a goal of treatment.

Key words

Graves’ ophthalmopathy - euthyroidism - hyperthyroidism - hypothyroidism - radioiodine

• References

• 1 Tallstedt L, Lundell G, Torring O et al. Occurrence of ophthalmopathy after treatment for Graves’ hyperthyroidism. The Thyroid Study Group. N Engl J Med 1992; 326: 1733-1738
• 2 Bartalena L, Marcocci C, Bogazzi F et al. Relation between therapy for hyperthyroidism and the course of Graves’ ophthalmopathy. N Engl J Med 1998; 338: 73-78
• 3 Kung AW, Yau CC, Cheng A. The incidence of ophthalmopathy after RAI therapy for Graves’ disease: prognostic factors and the role of methimazole. J Clin Endocrinol Metab 1994; 79: 542-546
• 4 Acharya SH, Avenell A, Philip S et al. Radioiodine therapy for Graves’ disease and the effect on ophthalmopathy – a systematic review. Clin Endocrinol (Oxf) 2008; 69: 943-950
• 5 Bahn RS, Burch HB, Cooper DS et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011; 21: 593-646
• 6 Chen DY, Schneider PF, Zhang XS et al. Striving for euthyroidism in radioiodine therapy of Graves’ disease – A 12-year prospective, randomized, open-label blinded end point study. Thyroid 2011; 21: 647-653
• 7 Chen DY, Jing J, Schneider PF et al. Comparison of the long-term efficacy of low dose ¹³¹I versus antithyroid drugs in the treatment of hyperthyroidism. Nucl Med Comm 2009; 30: 160-168
• 8 Bai Y. Thyroid disease study – basic and clinical. Beijing: Scientific and Technical Documents Publishing House 2003 (Chinese); 2003: 477
• 9 Mourits MP, Prummel MF, Wiersinga WM et al. Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol (Oxf) 1997; 47: 9-14
• 10 Prummel MF, Wiersinga WM, Mourits MP et al. Effect of abnormal thyroid function on the severity of Graves’ ophthalmopathy. Arch Intern Med 1990; 150: 1098-1101
• 11 Tallstedt L, Lundell G, Blomgren H et al. Does early administration of thyroxine reduce the development of Graves’ ophthalmopathy after radioiodine treatment. Eur J Endocrinol 1994; 130: 494-497
• 12 Perros P, Kendall-Taylor P, Neoh C et al. A prospective study of the effects of radioiodine therapy for hyperthyroidism in patients with minimally active graves’ ophthalmopathy. J Clin Endocrinol Metab 2005; 90: 5321-5323
• 13 Träisk F, Tallstedt L, Abraham-Nordling M et al. Thyroid-associated ophthalmopathy after treatment for Graves’ hyperthyroidism with antithyroid drugs or iodine-131. J Clin Endocrinol Metab 2009; 94: 3700-3707
• 14 Sridama V, McCormick M, Kaplan EL et al. Long-term follow-up study of compensated low-dose 131I therapy for Graves’ disease. N Engl J Med 1984; 311: 426-432
• 15 Ponto KA, Zang S, Kahaly GJ. The tale of radioiodine and Graves’ ophthalmopathy. Thyroid 2010; 20: 785-793
• 16 Laurberg P, Wallin G, Tallstedt L et al. TSH-receptor autoimmunity in Graves’ disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study. Eur J Endocrinol 2008; 158: 69-75
• 17 Abe Y, Sato H, Noguchi M et al. Effect of subtotal thyroidectomy on natural history of ophthalmopathy in Graves’ disease. World J Surg 1998; 22: 714-717
• 18 Fernández Sánchez JR, Rosell Pradas J, Carazo Martinez O et al. Graves’ ophthalmopathy after subtotal thyroidectomy and radioiodine therapy. Br J Surg 1993; 80: 1134-1136
• 19 Santos RB, Romaldini JH, Ward LS. A randomized controlled trial to evaluate the effectiveness of 2 regimens of fixed iodine (131I) doses for Graves’ disease treatment. Clin Nucl Med 2012; 37: 241-244